The similarity of the three-dimensional structure in the NAD-binding domain within the family of dehydrogenases is a familiar concept. An attempt has been made to correlate the structure-function relationship to the thermodynamics of coenzyme binding to several dehydrogenases. The delta G degree, delta H degree and delta S degree parameters are broadly similar for the binding of NAD(H) to yeast alcohol dehydrogenase, beef heart and rabbit muscle lactic dehydrogenase and pig heart malate dehydrogenase differing only within a range of 2 Kcal/mol in delta H degree and compensated by corresponding entropy changes resulting in minimal differences in delta G degree. However, in the case of horse liver alcohol dehydrogenase the delta H degree values of binding of NAD and NADH are close to zero, the contribution to the binding coming solely from entropic changes. This is suggestive of conformational changes in the enzyme upon binding NAD(H). This view is further confirmed by the thermodynamic parameters of ADP-Ribose binding to the enzymes wherein abnormality with respect to liver alcohol dehydrogenase vanishes. This study confirms the conclusions about the community of the topography of the NAD-binding domain in several dehydrogenases, and establishes that termodynamics can reflect structure-function correlation with respect to ligand binding.